Use of selective serotonin reuptake inhibitors may be associated with a faster rate of loss of bone density in older men and women, according to two articles in the June 25 issue of Archives of Internal Medicine.

Selective serotonin reuptake inhibitors (SSRIs) treat depression by inhibiting the protein that transports serotonin into neurons after a nerve impulse has passed across the synapse. This protein has recently been discovered in bone as well, raising the possibility that the antidepressants may affect bone density and risk of fracture.

In the first article, Susan J. Diem, MD, MPH, University of Minnesota, Minneapolis, and colleagues studied 2,722 older women (average age, 78.5 years) for three years (1997-1999). At that time and again an average of 4.9 years later, researchers measured women’s total hip bone density and also the density of two subregions.

At each visit, participants were asked to bring in all medications they had used within the past two weeks.

A total of 198 (7.3 percent) of the women used a member of that drug class, 118 (4.3 percent) took tricyclic antidepressants, and 2,406 (88.4 percent) took neither type of antidepressant (those who took both were not included in the analysis). After researchers adjusted for other factors affecting bone density and antidepressant use, including depression severity and calcium supplement use, bone mineral density at the hip was decreased by 0.82 percent in users of selective serotonin reuptake inhibitors. This compared with a decrease of 0.47 percent among women who used tricyclic antidepressants and also in women who did not take any antidepressant. Higher rates of bone loss were also observed at the two hip subregions among SSRI users.

“One potential explanation for our findings is that SSRI use may have a direct deleterious effect on bone,” the authors wrote. “This theory is supported by findings of in vitro and in vivo laboratory investigations.” Some data suggest that SSRIs may interfere with the function of osteoclasts and osteoblasts, cells responsible for the regular breaking down and rebuilding bone tissue.

“Our findings suggest that, in this cohort, use of SSRIs is associated with increased rates of hip bone loss,” the authors concluded. Although some of this association may have occurred because women who were prescribed SSRIs were different from those who were not prescribed SSRIs, “further investigation of SSRI use and rates of change in bone mineral density in other populations with longer follow-up is warranted given the recent description of serotonin transporters in bone.”

In a related paper, Elizabeth M. Haney, MD, of Oregon Health & Sciences University, Portland, and colleagues conducted a similar study with 5,995 men age 65 years and older (average age 73.7 years). The men’s bone density at the hip, including subregions, and at the base of the spine were measured between 2000 and 2002. Participants were asked to bring all medications to clinic visits, where they were also given a physical examination and asked about other health and lifestyle factors.

A total of 160 (2.7 percent) men reported using SSRIs, 99 (1.7 percent) reported using tricyclic antidepressants and 52 (0.9 percent) reported using trazodone, a third type of antidepressant. Total hip bone mineral density was 3.9 percent lower among SSRI users than among men who did not use an antidepressant. Similarly, spine bone mineral density was 5.9 percent lower among SSRI users than among non-users. There was no significant difference in either hip or spine density between men who took tricyclic antidepressants or trazodone and those who did not take antidepressants.

“These associations are biologically plausible and clinically important,” the authors concluded. “Because SSRI use is prevalent in the general population, our findings have a potentially important public health impact. If confirmed, people using SSRIs might be targeted for osteoporosis screening and preventive intervention.”